Lipopolysaccharide and anionic phospholipids in the Gram-negative bacterial outer membrane (LPS) (LPS)

Lipopolysaccharide (LPS) and anionic phospholipids are fundamental structural components of the outer membrane of Gram-negative bacteria, providing a formidable permeability barrier against environmental threats and antibiotics (Raetz & Whitfield, 2002, Annu Rev Biochem). LPS, often referred to as endotoxin, is composed of a hydrophobic Lipid A anchor, a core oligosaccharide, and a distal O-antigen (Bertani & Ruiz, 2018, Cold Spring Harb Perspect Biol). These molecules are essential for bacterial viability and serve as the primary target for polymyxin antibiotics, such as Colistin and Polymyxin B, which are considered last-resort treatments for multi-drug resistant infections (Poirel et al., 2017, Clin Microbiol Rev). The mechanism involves electrostatic binding to the negatively charged phosphate groups of LPS and phospholipids, displacing stabilizing divalent cations (Mg2+ and Ca2+) and causing membrane disruption (Trimble et al., 2016, Cold Spring Harb Perspect Med). Clinically, the release of LPS into the systemic circulation triggers a massive inflammatory response through the TLR4/MD-2 complex, potentially leading to sepsis and septic shock (Steimle et al., 2016, Nat Rev Microbiol).

Other names

EndotoxinLipid ABacterial outer membrane lipidsGram-negative cell wall components

Drugs typically bind to the negatively charged phosphate groups of lipopolysaccharide and anionic phospholipids via electrostatic interactions, displacing divalent cations (calcium and magnesium) that stabilize the membrane, leading to membrane disruption and cell death (Trimble et al., 2016, Cold Spring Harb Perspect Med).